Eastern Kentucky University
Synthetic Developments Towards Ergovaline
Institution
Eastern Kentucky University
Faculty Advisor/ Mentor
Nathan Tice; Darren Smith
Abstract
Ergovaline is one of several ergot alkaloids categorized as an ergopeptine, consisting of a lysergic acid moiety linked to a tripeptide. These biologically active ergot alkaloids are secondary metabolites of endophytic fungi that infect plants, including tall fescue, a rugged grass native to Kentucky that serves as an ideal source of feed for horses and livestock. Even in minute amounts, consumption of ergovaline from infected grass has been known to result in devastating effects in these animals. Although several efficient synthetic pathways have been developed for lysergic acid, a complete synthesis of ergovaline has yet to be reported. By developing an efficient and cost-effective synthesis for ergovaline, this compound can be made available for further toxicological studies that extend to biochemistry, pharmaceuticals, agriculture, and other related fields. Our proposed synthesis of the ergovaline tripeptide involves a condensation of commercially available amino acids, followed by derivatization with pyruvic acid, and a ring closure step using a lysergic acid model and a Lewis acid catalyst. Analytical methods such as GC-MS are used to confirm stepwise preparation. Herein are described the synthetic methodologies and analytical techniques being used towards the formation of this important ergot alkaloid.
Synthetic Developments Towards Ergovaline
Ergovaline is one of several ergot alkaloids categorized as an ergopeptine, consisting of a lysergic acid moiety linked to a tripeptide. These biologically active ergot alkaloids are secondary metabolites of endophytic fungi that infect plants, including tall fescue, a rugged grass native to Kentucky that serves as an ideal source of feed for horses and livestock. Even in minute amounts, consumption of ergovaline from infected grass has been known to result in devastating effects in these animals. Although several efficient synthetic pathways have been developed for lysergic acid, a complete synthesis of ergovaline has yet to be reported. By developing an efficient and cost-effective synthesis for ergovaline, this compound can be made available for further toxicological studies that extend to biochemistry, pharmaceuticals, agriculture, and other related fields. Our proposed synthesis of the ergovaline tripeptide involves a condensation of commercially available amino acids, followed by derivatization with pyruvic acid, and a ring closure step using a lysergic acid model and a Lewis acid catalyst. Analytical methods such as GC-MS are used to confirm stepwise preparation. Herein are described the synthetic methodologies and analytical techniques being used towards the formation of this important ergot alkaloid.